Fibrotic chronic eosinophilic pneumonia: from inflammation to fibrosis and therapeutic implications.

Chronic eosinophilic pneumonia is a rare inflammatory lung disease that typically responds to systemic glucocorticoids but is frequently complicated by relapses and treatment-related toxicity. In recent years, monoclonal antibodies targeting the interleukin-5 (IL-5) pathway have emerged as effective glucocorticoid-sparing therapies in relapsing or glucocorticoid-dependent chronic eosinophilic pneumonia. Alongside these advances, a substantial proportion of patients develops progressive fibrotic changes over time, challenging the traditional view of chronic eosinophilic pneumonia as a fully reversible condition. This narrative review summarises current clinical evidence on the use of anti-IL-5/IL-5 receptor subunit α biologicals in chronic eosinophilic pneumonia, examines the emerging phenotype of fibrotic chronic eosinophilic pneumonia, and discusses the mechanistic links between eosinophilic inflammation and pulmonary fibrosis. We also review experimental and clinical data implicating eosinophils, type 2 cytokines, epithelial alarmins and extracellular traps in fibroblast activation and extracellular matrix deposition, providing a biological rationale for a continuum from inflammation to irreversible lung remodelling. Available data on the use of IL-5-targeted therapies in fibrotic disease are limited, and no prospective studies have specifically addressed this patient population. Conversely, antifibrotic agents such as nintedanib have demonstrated efficacy in progressive fibrosing interstitial lung diseases but have been rarely studied in eosinophilic lung disorders. We propose a phenotype-adapted therapeutic framework in which sustained control of eosinophilic inflammation aims to prevent fibrotic progression in early disease, while antifibrotic therapy may be considered in patients with established or progressive fibrosis. Fibrotic chronic eosinophilic pneumonia thus represents a clinical entity at the crossroads between inflammation and fibrosis, requiring individualised management strategies and dedicated future studies.